Tacrolimus-loaded Drug Delivery Systems in Vascularized Composite Allotransplantation: Lessons and Opportunities for Local Immunosuppression.

Long-term systemic immunosuppression is needed for vascularized composite allotransplantation (VCA). The high rate of acute rejection episodes in the first posttransplant year, the development of chronic rejection, and the adverse effects that come along with this treatment, currently prevent a wider clinical application of VCA. Opportunistic infections and metabolic disturbances are among the most observed side effects in VCA recipients. To overcome these challenges, local immunosuppression using biomaterial-based drug delivery systems (DDS) have been developed. The aim of these systems is to provide high local concentrations of immunosuppressive drugs while reducing their systemic load. This review provides a summary of recently investigated local DDS with different mechanisms of action such as on-demand, ultrasound-sensitive, or continuous drug delivery. In preclinical models, ranging from rodent to porcine and nonhuman primate models, this approach has been shown to reduce systemic tacrolimus (TAC) load and adverse effects, while prolonging graft survival. Localized immunosuppression using biomaterial-based DDS represents an encouraging approach to enhance graft survival and reduce toxic side effects of immunosuppressive drugs in VCA patients. Preclinical models using TAC-releasing DDS have demonstrated high local immunosuppressive effects with a low systemic burden. However, to reduce acute rejection events in translational animal models or in the clinical reality, the use of additional low-dose systemic TAC treatment may be envisaged. Patients may benefit through efficient graft immunosuppression and survival with negligible systemic adverse effects, resulting in better compliance and quality of life.

Free Tissue Transfer in Head and Neck Reconstruction: A Multidisciplinary 15-Year Experience.

BACKGROUND: Free tissue transfer is considered the gold standard in reconstruction of extensive defects in head and neck surgery. The aim of this 15-year retrospective study is to analyze the outcomes of free tissue transfers in the head and neck area in a tertiary referral university hospital. MATERIALS AND METHODS: A retrospective, single-center study of all patients undergoing free tissue transfers for head and neck reconstruction between 2006 and 2020 was performed. Patient demographics, comorbidities, flap characteristics, outcomes and complications were assessed. RESULTS: A total of 353 free flaps were performed. The most common defect etiology was synchronous oncologic resection (74.2%). The majority of patients had at least one comorbidity (70.3%), with smoking recorded in 46.2% of the cases and alcohol consumption in 31.7%. The anterolateral thigh flap was the most commonly used flap (37.7%), followed by the osteoseptocutaneous fibula flap (26.9%). Our overall flap success rate was 97.7%, while the overall complication rate was 45.9%. CONCLUSIONS: Free tissue transfer in head and neck reconstruction is reliable. However, complication rates remain high due to the complexity of such cases and frequent presence of comorbidities. Nonetheless, when effectively managed within a multidisciplinary team, complications rarely jeopardize the overall reconstruction outcome.

Challenges and opportunities in vascularized composite allotransplantation of joints: a systematic literature review.

Background: Joint allotransplantation (JA) within the field of vascularized composite allotransplantation (VCA) holds great potential for functional and non-prosthetic reconstruction of severely damaged joints. However, clinical use of JA remains limited due to the immune rejection associated with all forms of allotransplantation. In this study, we aim to provide a comprehensive overview of the current state of JA through a systematic review of clinical, animal, and immunological studies on this topic. Methods: We conducted a systematic literature review in accordance with the PRISMA guidelines to identify relevant articles in PubMed, Cochrane Library, and Web of Science databases. The results were analyzed, and potential future prospects were discussed in detail. Results: Our review included 14 articles describing relevant developments in JA. Currently, most JA-related research is being performed in small animal models, demonstrating graft survival and functional restoration with short-term immunosuppression. In human patients, only six knee allotransplantations have been performed to date, with all grafts ultimately failing and a maximum graft survival of 56 months. Conclusion: Research on joint allotransplantation has been limited over the last 20 years due to the rarity of clinical applications, the complex nature of surgical procedures, and uncertain outcomes stemming from immune rejection. However, the key to overcoming these challenges lies in extending graft survival and minimizing immunosuppressive side effects. With the emergence of new immunosuppressive strategies, the feasibility and clinical potential of vascularized joint allotransplantation warrants further investigation.

Flap Reconstruction Outcome Following Surgical Resection of Soft Tissue and Bone Sarcoma in the Setting of (Neo)adjuvant Therapy: A Sarcoma Center Experience.

BACKGROUND: Soft tissue and bone sarcomas are heterogeneous groups of malignant tumors. The shift in their management, with an emphasis on limb salvage, has deemed the involvement of reconstructive surgeons an integral part of their multidisciplinary treatment. We present our experience with free and pedicled flaps in the reconstruction of sarcomas at a tertiary referral university hospital and major sarcoma center. MATERIALS AND METHODS: All patients undergoing flap reconstruction after sarcoma resection over a 5-year period have been included in the study. Patient-related data and postoperative complications were collected retrospectively, ensuring a minimum follow-up of 3 years. RESULTS: A total of 90 patients underwent treatment with 26 free flaps and 64 pedicled flaps. Postoperative complications occurred in 37.7% of patients, and the flap failure rate was 4.4%. Diabetes, alcohol consumption and male gender were associated with increased early necrosis of the flap. Preoperative chemotherapy significantly increased the occurrence of early infection and late dehiscence, while preoperative radiotherapy was associated with a higher incidence of lymphedema. Intraoperative radiotherapy was associated with late seromas and lymphedema. CONCLUSIONS: Reconstructive surgery with either pedicled or free flaps is reliable, but it can be demanding in the setting of sarcoma surgery. A higher complication rate is to be expected with neoadjuvant therapy and with certain comorbidities.

The osteocutaneous SCIP flap: A detailed description of the surgical technique and retrospective cohort study of consecutive cases in a tertiary European centre.

INTRODUCTION: In the era of increasing popularity of the superficial circumflex iliac perforator (SCIP) flap, osteocutaneous variants of the flap have been described as well. Despite their benefits such as customizability and low donor site morbidity, these flaps have not yet gained broad acceptance. By reviewing our case series, we aim to promote the safe application of this promising new tool in osteoplastic reconstructions. PATIENTS AND METHODS: We performed a single-centre, retrospective chart review of all cases in which osteocutaneous SCIP-flaps were used. We describe our surgical technique and present the surgical, functional and aesthetic outcomes of the patients in our cohort. RESULTS: Since September 2019, we have used osteocutaneous SCIP flaps in six patients, five in the extremities and one for the head and neck region. The vascularised bone segment was measured on average 4.9 cm (range 4-7 cm) x 3 cm (range 1.5-4 cm) and was combined with a skin paddle of a mean length of 14.3 cm (range 8-20 cm) and width of 6.3 cm (range 5-8 cm). One flap underwent emergency revision due to venous congestion. All flaps survived and healed uneventfully. Long-term follow-up shows adequate bony integration and stable soft tissue coverage with good functional restoration and minimal donor site morbidity. CONCLUSION: The osteocutaneous SCIP flap provides a large and thin skin island and a "moderately sized" vascularised bone segment with minimal donor site morbidity and can be successfully used in selected cases of osteoplastic reconstruction.

Schwannomas mistaken for metastases of melanoma in PET-CT: A diagnostic challenge with consequences.

The incidence of skin cancer and especially cutaneous malignant melanoma is rising, as are indications for staging examinations to detect metastasis. Schwannomas are common benign nerve tumors, which can be mistaken for metastasis even in highly specialized imaging. Risk of nerve lesion is high in inadvertent biopsy.

Management of Postoperative Seroma: Recommendations Based on a 12-Year Retrospective Study.

Introduction: Seroma formation is a serious postoperative complication. Since the management algorithms available in the literature are scarce, we aimed to analyze our experience with postoperative seroma in order to identify indicators for revisional surgery and propose recommendations for management. Methods: This retrospective study included all patients with postoperative seroma treated in a tertiary university hospital from 2008 to 2020. Patients' demographics, medical history, and seroma treatment details were recorded and analyzed. Results: Overall, 156 patients were included: 41% were initially treated through needle aspiration, with 61% eventually undergoing surgical treatment for postoperative seroma. Comorbidities, such as heart failure and coronary heart disease, were significantly associated with an increased need for revisional surgery (p < 0.05). Both a duration of >40 days of repeated needle aspirations and drain re-insertions were significantly correlated with an increased risk for revisional surgery (p < 0.05). Conclusion: Patients requiring seroma aspiration should be counseled on surgical treatment sooner rather than later, as prolonged aspiration time (over 40 days) greatly increases the risk of surgical revision. Moreover, the reinsertion of a drain should only be used as a temporizing measure, at most, and patients requiring a drain to control the size of the seroma should promptly be scheduled for a surgical revision.

Transcutaneous sentinel lymph node detection in cutaneous melanoma with indocyanine green and near-infrared fluorescence: A diagnostic sensitivity study.

Sentinel lymph node (SLN) biopsy with preoperative radiocolloid-based lymphoscintigraphy and blue dye injection is considered the standard procedure for staging nodal metastases in early-stage cutaneous melanoma patients with clinically uninvolved lymph nodes. While this combination renders good accuracy in SLN detection, radiation exposure and the frequent allergic reactions to the blue dye are considered drawbacks of this technique. Indocyanine green (ICG) is a water-soluble fluorescent dye that can be identified through near-infrared fluorescence imaging (NIRFI). The aim of this prospective diagnostic sensitivity study was to assess the feasibility of ICG and NIRFI to identify SLNs in melanoma transcutaneously ("before skin incision") and to analyze the various factors influencing detection rate, in comparison to lymphoscintigraphy. This study included 93 patients undergoing SLN biopsy for cutaneous melanoma. The region and the number of the SLNs identified with lymphoscintigraphy and with ICG were recorded. Patients' characteristics, as well as tumor details were also recorded preoperatively. One hundred and ninety-four SLNs were identified through lymphoscintigraphy. The sensitivity of ICG for transcutaneous identification of the location of the SLNs was 96.1% overall, while the sensitivity rate for the number of SLNs was 79.4%. Gender and age did not seem to influence detection rate, but a body mass index >30 kg/m2 was associated with a lower identification rate of the number of SLNs (P = .045). Transcutaneous identification of SLNs through ICG and NIRFI technology is a feasible technique that could potentially replace in selected patients the standard SLN detection methodology in cutaneous melanoma.

Post-bariatric contour deformity correction: an endeavour to establish objective criteria nationally.

BACKGROUND: A marked increase in bariatric surgery has led to higher numbers of patients with contour deformities after massive weight loss seeking plastic surgical correction. Insurance coverage for these post-bariatric interventions is highly subjective and a common set of objective criteria has not yet been established. AIM: The aim was to evaluate the factors influencing insurance coverage for post-bariatric surgery, focusing on finding objective, reproducible criteria. METHODS: This was a retrospective single centre chart review of all post-bariatric patients with redundant skin requesting body contouring surgery from 2013 to 2018. Demographic, bariatric and surgical, as well as insurance information were collected. A logistic regression model was used to identify predictors of successful insurance coverage. RESULTS: 116 Patients were included in the study. Insurance approval for post-bariatric body contouring surgery was obtained for only 47 patients (41%). Mentioning the term "medical indication" in the application letter was associated with a 15.2 times higher rate of receiving a positive answer (p <0.001), whereas mentioning "mental suffering" was associated with 82.3% lower chance of getting a positive response (p <0.001). A high body mass index (BMI) (p <0.009) before the bariatric operation as well as a high BMI reduction (p <0.021) were associated with a higher approval rate by insurance companies . An additional application letter to the insurance company (p <0.024) as well as mentioning mechanical restriction (p <0.022) were associated with a positive response from the insurance companies. CONCLUSIONS: We were able to establish certain objective predictive criteria for insurance coverage of post-bariatric surgery. However, it appears that the decisions of insurance companies for this condition are still rather randomly taken. Therefore, the establishment of objective criteria for insurance coverage may allow fairer treatment for this growing patient population.

Coverage of complex tissue defects following open cervicothoracic spine surgery with a lower trapezius island myocutaneous flap-an interdisciplinary approach.

The study design is a clinical case series. The objective of this study was to present the concept and efficacy of the lower trapezius island myocutaneous flap (LTIMF) for management of complex wound healing disorders following open cervicothoracic spine surgery. Wound healing disturbances with myocutaneous defects after open spine surgery at the cervical and upper thoracic spine are well-described complications. In severe cases, plastic reconstructive coverage is often required as a last resort. A review of all adult patients with deep wound dehiscence and tissue defects following open cervicothoracic spine surgery, who were managed with plastic surgery reconstruction using a LTIMF at our institution, was conducted. Synopses of these cases are presented. Seven patients with a mean age of 73 years ± 13 (range 50 to 89 years) were included in this case series. Six out of seven patients had instrumented posterior fusion added to their decompression. All patients were managed with a LTIMF for wound coverage. No spinal implants were removed prior to LTIMF surgery. The mean follow-up was 5.2 months (± 5.4 months). No major flap failure occurred, and all patients presented with satisfactory cosmetic results. The only minor complication was development of a sterile subcutaneous seroma in two patients, which were successfully managed by puncture and aspiration. The LTIMF is an effective and reliable salvage treatment option for spine surgery patients offering stable coverage of deep tissue defects resulting from complex wound healing disorders at the cervical and upper thoracic spine.

Presence of Donor Lymph Nodes Within Vascularized Composite Allotransplantation Ameliorates VEGF-C-mediated Lymphangiogenesis and Delays the Onset of Acute Rejection.

BACKGROUND: The lymphatic system plays an active role in modulating inflammation in autoimmune diseases and organ rejection. In this work, we hypothesized that the transfer of donor lymph node (LN) might be used to promote lymphangiogenesis and influence rejection in vascularized composite allotransplantation (VCA). METHODS: Hindlimb transplantations were performed in which (1) recipient rats received VCA containing donor LN (D:LN+), (2) recipient rats received VCA depleted of all donor LN (D:LN-), and (3) D:LN+ transplantations were followed by lymphangiogenesis inhibition using a vascular endothelial growth factor receptor-3 (VEGFR3) blocker. RESULTS: Our data show that graft rejection started significantly later in D:LN+ transplanted rats as compared to the D:LN- group. Moreover, we observed a higher level of VEGF-C and a quicker and more efficient lymphangiogenesis in the D:LN+ group as compared to the D:LN- group. The presence of donor LN within the graft was associated with reduced immunoactivation in the draining LN and increased frequency of circulating and skin-resident donor T regulatory cells. Blocking of the VEGF-C pathway using a VEGFR3 blocker disrupts the lymphangiogenesis process, accelerates rejection onset, and interferes with donor T-cell migration. CONCLUSIONS: This study demonstrates that VCA LNs play a pivotal role in the regulation of graft rejection and underlines the potential of specifically targeting the LN component of a VCA to control graft rejection.

Mixed Metal Oxide Nanoparticle Formulations for the Treatment of Seroma.

Seroma formation is a well-recognized postoperative complication for many plastic and general surgical procedures. Although various tissue adhesives and substances have been used in an effort to treat seroma formation, no therapies have been established clinically. Recently, the nano-bridging phenomenon has been introduced as a promising approach to achieve tissue adhesion and strong closure of deep skin wounds in rats. The present study seeks to assess the potential of nano-bridging beyond skin wounds in a rat model of seroma. Seromas were induced in 20 Lewis rats through bilateral axillary lymphadenectomy, excision of the latissimus dorsi and cutaneous maximus muscles, and disruption of dermal lymphatics. On postoperative day (POD) 7, the seroma was aspirated on both sides. A bioactive nanoparticle (NP) suspension based on zinc-doped strontium-substituted bioglass/ceria nanoparticles (NP group) or fibrin glue (fibrin group) was injected into the right seroma cavity, while the left side was left untreated. On POD 14, the NP group showed complete remission (no seromas at all), while the fibrin group recorded a reduction of only 63% in the seroma fluid volume. The NPs exerted local anti-inflammatory and neo-angiogenic effects, without any detectable systemic changes. Moreover, the ceria levels recorded in the organs did not surpass the background level, indicating that the nanoparticles stayed at the site of application. This study is a promising first example demonstrating the ability of inorganic nanoparticle formulations to reduce seroma formation in a rat model, without any detectable systemic adverse effects. These results emphasize the potential of nanotechnological solutions in the therapeutic management of seroma in the clinical setting.

Perioperative predictors of early surgical revision and flap-related complications after microvascular free tissue transfer in head and neck reconstructions: a retrospective observational series.

OBJECTIVES: The aim of this study was to determine the influence of perioperative fluid management and administration of vasopressors on early surgical revision and flap-related complications in free tissue transfer. MATERIALS AND METHODS: Intraoperative amount of fluid and of vasopressors, relevant perioperative parameters, and comorbidities were recorded in 131 patients undergoing head and neck microvascular reconstruction and compared with early surgical complications, defined as interventions requiring surgery after a flap-related complication, and/or other surgical problems in the operating room within 30 days after initial surgery. The relationship between perioperative variables for each revision category was determined using an optimized multiple logistic regression. RESULTS: The administration of diuretics (p=0.001) as a treatment for perioperative fluid overload and the type of flap (p=0.019) was associated with a higher risk of early surgical revisions. Perioperative fluid overload (p=0.039) is significantly related to flap-related complications. We found no effect of intraoperative administration of vasopressors on early surgical revisions (p=0.8) or on flap-related complications (norepinephrine p=0.6, dobutamine p=0.5). CONCLUSION: Perioperative fluid overload is associated with higher risks of early surgical revision and flap-related complications. In contrast, the administration of vasopressors seemed to have no effect on either surgical revision rate or flap-related complications. CLINICAL RELEVANCE: In patients receiving microvascular reconstructions, a balanced fluid administration perioperatively and a targeted use of vasopressors should be the necessary strategy to reduce the complication rates in head and neck surgery.

The anatomical reliability of the superficial circumflex iliac artery perforator (SCIP) flap.

INTRODUCTION: In order to achieve a satisfactory functional and aesthetic result a thin skin flap is often required in surgical reconstruction of various body regions. Perforator flaps based on either the superficial or deep branch of the superficial circumflex iliac artery (SCIA) have been used for this purpose mainly in the Asian population. Recently the superficial plane has been established as a new way of elevating the flap. Anatomical studies and details of this new flap are lacking. MATERIAL AND METHODS: Wide areas were harvested subfascially from the groin of Thiel-fixated cadavers. Both deep and superficial branches of the superficial circumflex iliac artery were carefully dissected and individually injected with µAngiofil. After CT-imaging the flaps were raised on the superficial plane, perforators were marked and the flaps subsequently rescanned. High-resolution images of regions of interest were taken using micro-CT. RESULTS: A total of 21 flaps were harvested and analyzed. Both the deep and superficial branch provided more than three perforators per branch, however, the deep branch based flap was significantly larger (202 vs. 112 cm2, p < 0.01) and had a longer pedicle (9.1 vs. 6.6 cm, p < 0.01). Raising the flap in the superficial plane reliably reduces bulk and increases homogeneity. CONCLUSIONS: The SCIP flap appears to have a reliable vascular blood supply. The SCIA and its main branches and perforators have a consistent vascular pattern. The deep branch of the SCIA has the anatomic potential to be the preferred pedicle in case larger flaps with longer pedicles are necessary.

Predicting risk factors that lead to free flap failure and vascular compromise: A single unit experience with 565 free tissue transfers.

BACKGROUND: Even though the benefit of free tissue transfer is uncontested in complex reconstructive cases, vascular compromise and/or flap failure remain a challenge for the surgeon and identification of possible risk factors can aid in the preoperative planning. The aim of this study was to identify the individual risk factors leading to flap failure and/or vascular compromise in free tissue transfers in a single institution over a period of 10 years and to create an index predicting these problems, as well as finding predictors of other postoperative complications. METHODS: Data from all the patients undergoing free tissue transfers between 2009 and 2018 were retrospectively analyzed (demographics, comorbidities, flap failure, vascular compromise, and other complications). The results from the univariate and multivariate analyses were used to create an index. RESULTS: A predictability index with three classes (low, moderate, and high risk) was calculated for each patient, based on defect etiology and the presence of coronary heart disease, diabetes, smoking, peripheral arterial vascular disease, and arterial hypertension. A patient with moderate-risk index had 9.3 times higher chances of developing vascular compromise than those in the low-risk group, while a high-risk index had 18.6 higher odds (p=0.001). American Society of Anesthesiologists (ASA) classification was found to be a predictor of complications in free tissue transfer (p=0.001). CONCLUSION: If patients at a high risk of vascular compromise could be identified preoperatively through this predictability index, patient counseling could be improved and the surgeon might adapt the reconstructive plan and choose an alternative reconstructive strategy.

Development of vascularized nerve scaffold using perfusion-decellularization and recellularization.

INTRODUCTION: Vascularized nerve grafts (VNG) may offer an advantage in peripheral nerve regeneration by avoiding ischemic damage and central necrosis observed in non-VNG, particularly for the treatment of large and long nerve defects. However, surgical complexity, donor site morbidity and limited nerve availability remain important drawbacks for the clinical use of VNG. Here we explore the potential of perfusion-decellularization for bioengineering a VNG to be used in peripheral nerve reconstruction. METHODS: Porcine sciatic nerves were surgically procured along with their vascular pedicle attached. The specimens were decellularized via perfusion-decellularization and preservation of the extracellular matrix (ECM), vascular patency and tissue cytokine contents were examined. Scaffold reendothelialization was conducted with porcine aortic endothelial cells in a perfusion-bioreactor. RESULTS: Morphologic examination of decellularized VNG and analysis of the DNA content demonstrated cell clearance whereas ECM content and structures of the nerve fascicles were preserved. Using 3D micro-computed tomography imaging we observed optimal vasculature preservation in decellularized scaffolds, down to the capillary level. Cytokine quantification demonstrated measurable levels of growth factors after decellularization. Endothelial cell engraftment of the large caliber vessels was observed in reendothelialized scaffolds. CONCLUSIONS: In this study we provide evidence that perfusion-decellularization can be used to create vascularized nerve scaffolds in which the vasculature and the ECM component are well preserved. As compared to non-vascularized conduits, engineered vascularized nerve scaffolds may represent an ideal approach for promoting better nerve regeneration in larger nerve defect reconstructions.

Regional Lymphatic Inclusion in Orthotopic Hindlimb Transplantation: Establishment and Assessment of Feasibility in a Rodent Model.

BACKGROUND: The lymphatic system may play an important role in local immunomodulation in vascularized composite allotransplantation (VCA). Currently, there is no standardized VCA model that includes the regional draining lymphatic tissue. The aim of this study was to develop a rapid and efficient orthotopic hindlimb transplantation model in rats that included the draining lymphatic basin to permit further evaluation of the lymphatic system's role in VCA. METHODS: Thirty transplantations from Brown Norway rats to Lewis rats were performed. To include the regional lymphatic tissue, the superficial epigastric vessels were preserved to allow retrieval of the corresponding inguinal lymph nodes, including the inguinal fat pad, with the hindlimb. A cuff technique was used for the vein, whereas the conventional microsurgical technique was used for the arterial anastomosis. Vascular patency was confirmed through laser Doppler analysis at postoperative day 1 and histological analysis after euthanasia. RESULTS: The presence and vascularization of the inguinal lymph nodes were verified with indocyanine green lymphoscintigraphy at the time of transplantation. Mean total ischemia time was 69 ± 24 minutes, and mean recipient operation time was 80 ± 19 minutes. Overall transplant survival rate was 93.3%. Laser Doppler analysis showed vascular (technical) success, indocyanine green lymphoscintigraphy confirmed the presence of lymph nodes and the histological analysis revealed patent anastomoses. CONCLUSIONS: We successfully developed an experimental orthotopic hindlimb transplantation model in rats that includes the draining inguinal lymphatic basin, which is an important asset in further research on lymphatic tissue and its role in VCA.

Multiscale Analysis of Metal Oxide Nanoparticles in Tissue: Insights into Biodistribution and Biotransformation.

Metal oxide nanoparticles have emerged as exceptionally potent biomedical sensors and actuators due to their unique physicochemical features. Despite fascinating achievements, the current limited understanding of the molecular interplay between nanoparticles and the surrounding tissue remains a major obstacle in the rationalized development of nanomedicines, which is reflected in their poor clinical approval rate. This work reports on the nanoscopic characterization of inorganic nanoparticles in tissue by the example of complex metal oxide nanoparticle hybrids consisting of crystalline cerium oxide and the biodegradable ceramic bioglass. A validated analytical method based on semiquantitative X-ray fluorescence and inductively coupled plasma spectrometry is used to assess nanoparticle biodistribution following intravenous and topical application. Then, a correlative multiscale analytical cascade based on a combination of microscopy and spectroscopy techniques shows that the topically applied hybrid nanoparticles remain at the initial site and are preferentially taken up into macrophages, form apatite on their surface, and lead to increased accumulation of lipids in their surroundings. Taken together, this work displays how modern analytical techniques can be harnessed to gain unprecedented insights into the biodistribution and biotransformation of complex inorganic nanoparticles. Such nanoscopic characterization is imperative for the rationalized engineering of safe and efficacious nanoparticle-based systems.

The effects of optimizing blood inflow in the pedicle on perforator flap survival: A pilot study in a rat model.

BACKGROUND: Perforator flaps have led to a revolution in reconstructive surgery by reducing donor site morbidity. However, many surgeons have witnessed partial flap necrosis. Experimental methods to increase inflow have relied on adding a separate pedicle to the flap. The aim of our study was to experimentally determine whether increasing blood flow in the perforator pedicle itself could benefit flap survival. METHODS: In 30 male Lewis rats, an extended posterior thigh perforator flap was elevated and the pedicle was dissected to its origin from the femoral vessels. The rats were assigned to three groups: control (group I), acute inflow (group II) and arterial preconditioning (group III) depending on the timing of ligation of the femoral artery distal to the site of pedicle emergence. Digital planimetry was performed on postoperative day (POD) 7 and all flaps were monitored using laser Doppler flowmetry perioperatively and postoperatively in three regions (P1-proximal flap, P2-middle of the flap, P3-distal flap). RESULTS: Digital planimetry showed the highest area of survival in group II (78.12%±8.38%), followed by groups III and I. The laser Doppler results showed statistically significant higher values in group II on POD 7 for P2 and P3. At P3, only group II recorded an increase in the flow on POD 7 in comparison to POD 1. CONCLUSIONS: Optimization of arterial inflow, regardless if performed acutely or as preconditioning, led to increased flap survival in a rat perforator flap model.